MDMA (ECSTASY) ENHANCES 5-HT1A RECEPTOR DENSITY AND 8-OH-DPAT-INDUCEDHYPOTHERMIA - BLOCKADE BY DRUGS PREVENTING 5-HYDROXYTRYPTAMINE DEPLETION

One week after a single administration of 3,4-methylenedioxymethamphet amine (MDMA.HCl, 30 mg/kg i.p.), 5-HT1A receptor density was significa ntly increased by approximately 25-30% in the frontal cortex and hypot halamus of rats. The increased density correlated with the potentiatio n of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy -2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or halo peridol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depl etion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked t he effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-D PAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyp erthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA-induced 5-HT loss also prevent the ch anges in 5-HT1A receptor density as well as the enhanced hypothermic r esponse to the 5-HT1A receptor agonist 8-OH-DPAT in MDMA-treated rats. (C) 1998 Elsevier Science B.V.